The role of connective tissue in maintaining the integrity of cardiovascular (C-V) structures is important in a variety of C-V disorders. Although connective tissue components of C-V structures have for the most part been identified, the precise mechanisms of their involvement in disease and their biologic functions remain obscure. This research evaluates the nature and chemistry of the carbohydrate macromolecules of C-V connective tissue and attempts to elucidate their part in the pathogenesis of C-V diseases, especially atherosclerosis, and vascular complications of diabetes mellitus. Studies will concern glycosaminoglycans, proteoglycans, and glycoproteins, and the interaction of these carbohydrate-protein macromolecules with lipoproteins and fibrous structures--collagen and elastin. Efforts will be made to improve the characterization of proteoglycans and glycoproteins found in the arterial wall. The interaction of proteoglycans with serum lipoproteins may be an important mechanism in the pathogenesis of atherosclerotic lesions responsible for sequestering serum lipoproteins. Further, interactions of specific proteoglycans with collagen and elastin will be studied as important mechanisms in maintaining the normal architecture of the arterial wall. In these studies human tissues and tissues obtained from experimental animals are used. Special studies of heparin and heparin-like compounds, being used as antiatherogenic agents, are being conducted. C-V connective tissue is a prime target for hormonal effects, although other factors, e.g., genetic and metabolic changes of the carbohydrate macromolecules, may be responsible for the development of C-V diseases. Therefore, other problems which have a high relationship to vascular disease, i.e., diabetes mellitus, are being studied at both clinical and experimental levels. The primary objective of the research is to define more precisely the role that specific connective tissue components play in the structural changes of C-V tissues with disease. Such information ultimately will improve approaches to treatment and prevention of heart disease.